Persistent infection of adult mink with the Aleutian mink disease parvovirus (ADV) leads to disturbances of immune regulation, including hypergammaglobulinemia, plasmacytosis, immune complex disease, interstitial and glomerulonephritis. The exceptionally high levels of antiviral antibody are not able to eliminate the virus, and in fact enhance infection of Fc-receptor bearing cells, like macrophages. We are studying ADV infection in vivo, in vitro and in an ex vivo system of gel supported lymph node histocultures. This year we further characterized the histoculture system. Pathogenic isolates of ADV can replicate in the cultures and produce infectious virus.We also studied outbreaks of ADV-induced neurological disease in ferrets and in mink. In both instances, the CNS tissue lesions were plasmacytic meningoencephalitis, suggesting an immunological basis to the disorder. ADV DNA was identified and sequenced. The sequence of the ferret ADV was similar to other isolates of ferret ADV, but the ADV from the mink encephalitis outbreak (ADV-TH) had several unique residues in the region of the capsid gene that governs pathogenicity. These studies indicate that ADV can cause immune mediated lesions in the nervous system. We do not yet know if this is a consequence of the virus isolate or the host response. - Parvoviruses, viral pathogenesis, lymphoid tissues, parvovirus B19, Aleutian mink disease parvovirus